Allogeneic Blood Stem Cell Transplantation and Adoptive Immunotherapy for Hodgkin's Disease
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Purpose
The goal of this clinical research study is to learn if fludarabine, melphalan and gemcitabine followed by transplantation of stem cells (blood-forming cells) as well as immune cells (lymphocytes), collected from a matched related (i.e. a sibling) or unrelated donor, or a mismatched related donor, can help to control Hodgkin's disease. The safety of the treatment will also be studied.
| Condition | Intervention | Phase |
|---|---|---|
|
Hodgkin's Disease |
Drug: Gemcitabine Drug: Fludarabine Drug: Melphalan Drug: Antithymocyte Globulin Procedure: Allogeneic Stem Cell Infusion |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Allogeneic Stem Cell Transplantation Followed By Adoptive Immunotherapy for Patients With Relapsed and Refractory Hodgkin's Disease |
- Transplant Related Mortality [ Time Frame: Transplant to 100 days post transplant ] [ Designated as safety issue: Yes ]
| Estimated Enrollment: | 70 |
| Study Start Date: | July 2005 |
| Estimated Primary Completion Date: | July 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Gemcitabine + Fludarabine + Melphalan
Gemcitabine 800 mg/m^2 IV Over 30 Minutes x 1 Day. Fludarabine 33 mg/m^2 IV. Melphalan 70 mg/m^2 IV Over 30 Minutes x 2 Days. Antithymocyte Globulin 2 mg/kg IV for two days before stem cell transplantation. If you are receiving a transplant from a matched unrelated donor (not a blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant. Infusion of stem cells on Day 0.
|
Drug: Gemcitabine
800 mg/m^2 IV Over 30 Minutes x 1 Day
Other Names:
Drug: Fludarabine
33 mg/m^2 IV Over 30 Minutes x 4 Days
Other Names:
Drug: Melphalan
70 mg/m^2 IV Over 30 Minutes x 2 Days
Drug: Antithymocyte Globulin
2 mg/kg IV for two days before stem cell transplantation. If you are receiving a transplant from a matched unrelated donor (not a blood relative), a mismatched related donor (a blood relative, but not a full match), or receiving a cord blood transplant. Other Names:
Procedure: Allogeneic Stem Cell Infusion
Infusion of stem cells on Day 0.
Other Names:
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Detailed Description:
The main drugs used in this study are fludarabine, melphalan and gemcitabine. Fludarabine is a drug designed to weaken the immune defenses in order to allow the body to accept donors' cells. Melphalan is a chemotherapy drug that weakens the immune system but also kills cancer cells present in the body. Gemcitabine is a chemotherapy drug that kills cancer cells present in the body.
If you are found to be eligible to take part in this study, you will have a plastic tube (catheter) inserted into a vein under the collarbone. Drugs, blood products, and stem cells will be given and taken through this tube.
Gemcitabine will be given by vein or through the catheter for one day. Fludarabine will be given through the catheter once a day for 4 days. You will also receive melphalan once daily for 2 days. If you are receiving a transplant from a matched unrelated donor (not a blood relative), a mismatched related donor (a blood relative, but not a full match), you will also receive antithymocyte globulin (ATG) once a day for 2 days. ATG is given to decrease the risk of graft-versus-host disease. Tacrolimus will also be given to all patients to decrease the risk of (or treat) graft-versus-host disease. All participants are expected to need blood transfusions as part of this treatment.
Beginning 2 days before the transplant, tacrolimus will be given through the catheter over 24 hours. This will be changed to pills once you can tolerate swallowing pills. If no active cancer is detected and there is no graft-versus-host disease, you will then swallow 1 or more tacrolimus pills a day for only about 3-4 months, instead of the usual period of 6 months. This is done to boost the donor immune system against the cancer.
On the transplant day ("Day 0"), the stem cells or bone marrow collected from the donor will be infused through the catheter ("transplant"). You will receive a mixture of stem cells and immune cells. Drugs such as corticosteroids, acetaminophen (Tylenol), and/or Benadryl will be given through the catheter, before the infusion, to decrease the chance of allergic reactions. Starting on Day 7 after the transplant, filgrastim (G-CSF) will be given as an injection under the skin or through a needle to increase the growth of white blood cells. Methotrexate, a chemotherapy drug, will be given in small doses through the catheter on Days 1,3,6, 11 after the transplant to decrease the risk of graft-versus-host disease (GVHD).
If you have persistent but stable (not "growing") disease after transplant, you will have your immunosuppressive medications (tacrolimus, corticosteroids) stopped even before 4 months. If there is no response, you will receive an infusion of additional cells from your donor. If you have progressive ("growing") Hodgkin's disease after the transplant, you will be taken off study, and other treatment options may be explored.
Blood, bone marrow, and x-ray examinations will be performed periodically to monitor the results of the bone marrow transplantation. Blood tests will usually require up to 3-4 tablespoons of blood. These examinations will be done before the transplant, before you are released to go back home (about 100 days after the transplant), and then as deemed necessary by your physician. Blood tests will be done daily while you are hospitalized and several times a week until your blood counts recover.
This is an investigational study. All of the drugs used in this study are FDA-approved and commercially available. Up to 70 patients will take part in this study. All will be enrolled at MD Anderson.
Eligibility| Ages Eligible for Study: | up to 65 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients < 65 years of age with histologically confirmed refractory or relapsed Hodgkin's disease (including patients who fail or relapse after autologous SCT). This upper age limit will apply to transplants from both matched related and unrelated donors.
- Patients should have any of the following disease status: a. responsive or stable disease on salvage chemotherapy or radiation therapy. b. untreated, smoldering (i.e. not rapidly progressive) relapses.
- Patients must have a serum bilirubin equal to or </=2.0 mg/dl (isolated hyperbilirubinemia related to Gilbert's disease allowed), serum transaminase (ALT) equal to or </= 3 times the upper limit of the normal range, serum creatinine <2.0 mg/dl (provided they also have a glomerular filtration rate of at least 55 ml/min), no symptomatic cardiac or pulmonary disease and a performance status equal to or </=2. Left ventricular ejection fraction >/= 40%, FEV1, FVC and DLCO >/= 50% predicted.
- Patients must have an HLA-compatible related or unrelated donor (one-antigen mismatched related donors are acceptable) willing to donate marrow or rhG-CSF-mobilized peripheral blood stem cells. In the event of transplants from matched unrelated donors, a high-resolution allele match for HLA-A, -B, -C, -DRB1 ("8 of 8 match") is required.
- Women of childbearing potential must have a negative serum pregnancy test within two weeks of study entry and should be advised to avoid becoming pregnant. Men should be advised to not father a child while on treatment. Both women of childbearing potential and men must agree to practice effective methods of contraception.
- Patients must be capable and willing to sign informed consent.
Exclusion Criteria:
- Patients with documented disease progression on salvage chemotherapy.
- Nursing or pregnant females. Should a woman become pregnant or suspect she is pregnant while participating in the study, she should inform her treating physician immediately.
- Severe concomitant medical or psychiatric illness.
- Uncontrolled arrhythmia or symptomatic cardiac or pulmonary disease.
- Chronic active hepatitis or cirrhosis.
- Active or uncontrolled infection.
- Radiation therapy involving chest (axilla excluded), mediastinum, or abdomen (i.e., small or large bowel) completed within 10 weeks of transplant admission. Radiation therapy shortly before the start of the preparative regimen is allowed.
- Prior or concurrent malignancies (including myelodysplasia) except resected basal cell carcinoma or treated carcinoma in-situ. Cancer treated with curative intent < 5 years previously will not be allowed unless approved by the Protocol Chair. Cancer treated with curative intent > 5 years previously will be allowed.
Contacts and Locations| Contact: Paolo Anderlini, MD | 713-792-8750 |
| United States, Texas | |
| UT MD Anderson Cancer Center | Recruiting |
| Houston, Texas, United States, 77030 | |
| Principal Investigator: Paolo Anderlini, MD | |
| Principal Investigator: | Paolo Anderlini, MD | M.D. Anderson Cancer Center |
More Information
Additional Information:
No publications provided
| Responsible Party: | M.D. Anderson Cancer Center |
| ClinicalTrials.gov Identifier: | NCT00385788 History of Changes |
| Other Study ID Numbers: | 2005-0015 |
| Study First Received: | October 9, 2006 |
| Last Updated: | April 29, 2013 |
| Health Authority: | United States: Institutional Review Board |
Keywords provided by M.D. Anderson Cancer Center:
|
Hodgkin's Disease Stem Cell Transplantation Antithymocyte Globulin Gemcitabine Gemzar Fludarabine Fludarabine Phosphate |
Melphalan Allogeneic stem cell transplantation AST SCT ATG Thymoglobulin |
Additional relevant MeSH terms:
|
Hodgkin Disease Lymphoma Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Antilymphocyte Serum Melphalan Gemcitabine Fludarabine monophosphate Fludarabine Vidarabine Immunosuppressive Agents |
Immunologic Factors Physiological Effects of Drugs Pharmacologic Actions Myeloablative Agonists Antineoplastic Agents Therapeutic Uses Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antimetabolites, Antineoplastic Antimetabolites Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Radiation-Sensitizing Agents |
ClinicalTrials.gov processed this record on May 23, 2013